Melanoma BRAF V600E/K MutatedPhase 1/2OPTIMUMNCT02202200
Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma
A Phase 1/2 study testing PD- 0332991 in people with Melanoma BRAF V600E/K Mutated and CDNKN2A Loss Defined, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
An open label multicentre, phase I-II study with tumour molecular pharmacodynamics (MPD) evaluation and pharmacokinetics of PD-0332991 added to vemurafenib in patients suffering metastatic melanoma with BR. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma BRAF V600E/K Mutated, CDNKN2A Loss Defined
- What is being tested?
- PD- 0332991
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- May 2014to Aug 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Stage IV or un-resectable stage III melanoma
- Presence of BRAF V600E/K mutation and CDNKN2A loss and expression of Rb using immunohistochemistry in a recent metastatic sample (< 6 months)
- A previous exposure to BRAF inhibitor or combination of BRAF and MEK inhibitors therapy is allowed unless it has been stopped more than 3 months before study enrolment(This will defined the two strata of the trial)
- No previous therapy by MEK inhibitor unless associated with BRAF inhibitors
- No previous therapy with the AKT/PI3K pathway inhibitor
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- Patients should have a tumour available for repeated biopsies for pharmacodynamics evaluation
- Life expectancy of > 3 months
- ECOG performance status <2
- Signed informed consent
- Patient with health insurance coverage
- No patient under guardianship or curators
Who cannot join
- Inadequate hepatic function defined as serum bilirubin>25 μmol/l, transaminases > 3.0 times the upper limit of normal (ULN) or 5ULN in cases of liver metastases;
- Inadequate bone marrow function defined as absolute neutrophil count<1500/mcl, platelets<150000/mcl and haemoglobin<8g/dL
- Inadequate renal function with serum creatinine>2.0mg/dl) and /or creatinine clearance< 60 ml/min
- Untreated brain metastases : Patients with brain metastases will be eligible if they have completed treatment 1 months prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 5 days, and are neurologically asymptomatic
- Myocardial infarct or unstable angina within the past 6 months
- Concomitant take of drugs known to be strong inhibitor or inducers of CYP314
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- HIV positive.
- Chemotherapy, immunotherapy within 4 weeks
- Drugs interfering with PD-0332991 and vemurafenib metabolism
- Malabsorption syndrome or other condition that would interfere with enteral absorption
- Congenital long QT syndrome or screening QTc > 470 msec
- Need for chronic corticosteroid therapy of ≥10 mg of prednisone per day
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Saint-Louis Hospital
Paris, Paris, 75010
Celeste Lebbe, MDPHD, +33 1 42 49 49 49, celeste.lebbe@sls.aphp.fr
celeste lebbe, MD-PHD
About this study
Official title: An Open Label Multicenter, Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma With BRAFv600 Mutated and CDKN2A Loss and Expression of Rb and Treated by Vemurafenib
An open label multicentre, phase I-II study with tumour molecular pharmacodynamics (MPD) evaluation and pharmacokinetics of PD-0332991 added to vemurafenib in patients suffering metastatic melanoma with BR.
The main objective is to establish the Maximum Tolerated Dose (MTD) of PD-0332991 when added to standard vemurafenib therapy (960 mg BID). The estimated MTD is defined as the dose of PD-0332991 combined with vemurafenib that will be associated with a prespecified proportion of patients experiencing a Dose-Limiting Toxicity (DLT), ie, 1/3.
- Being tested
- PD- 0332991
- Keywords
- Melanoma, BRAF mutated
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD- 0332991Drug
PD-0332991 Inhibitor of cyclin-dependant kinase (CDK) 8 schedules will be evaluated PD-0332991 PO QD either at 25 mg, 50 mg, 75 mg, 100 mg, 125 mg, 150 mg, 175 mg and 200 mg
All patients will receive vemurafenib as background therapy ,bid at 720mg bid for the first group (during the first 2 cycle then 960 mg bid if good tolerance) and 960mg bid for all other patients
| Study group | Role | What they receive |
|---|---|---|
| PD-0332991 | Experimental | Not described Receives: Drug: PD- 0332991 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence within the first 2 cycles of treatment of a DLT
DLTs, serious adverse events and adverse events leading to treatment discontinuations will be determined as follows:
- Any grade 3 or more non-haematological toxicity excluding:
- Grade 3 asymptomatic increase in liver function tests (AST, ALT, ALP) reversible within 7 days for subjects without liver involvement, or grade 4 for subjects with liver involvement.
- Grade 3 vomiting if it is encountered despite adequate and optimal therapy (e.g. 5HT3 antagonists and corticosteroids).
- Grade 3 diarrhoeas if encountered despite adequate and optimal anti diarrhoea therapy.
- Confirmed grade 3 QTc prolongation (QTc >500 msec) that persists after correction of other possible causes such as electrolyte imbalance
- Grade 4 hyperlipidemia if it is encountered despite adequate and optimal therapy.
- Any grade 4 neutropenia of > 5 days duration, or febrile neutropenia lasting for more than 1 day.
- Grade 4 thrombocytopenia > 1 day, or grade 3 with bleeding.
Measured: 42 Days
Secondary outcomes (3)
Efficacy
Occurrence of clinical benefit (defined as Complete Response (CR), Partial Response (PR) or stable disease (SD)) and progressive disease based on the best overall response which depends on the tumour evaluations assessed using RECIST at the end of each 2 cycles.
Measured: 42 Days
1 year survival rate
survival
Measured: 1 year
Tolerance
Occurrence of clinically significant changes in a laboratory parameter and/or vital signs judged to be related to the trial medication within the first 6 months.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2014 (estimated)
- Study startMay 2014
- Primary completionNov 2016 (estimated)
- Study completionAug 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Melanoma BRAF V600E/K MutatedStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02202200
- Sponsor's protocol ID
- D20121106
- Acronym
- OPTIMUM
- Status last verified
- Apr 2016
- First submitted
- 25 Jul 2014
- Last updated
- 18 Apr 2016
- Results posted
- No
Publications
Louveau B, Resche-Rigon M, Lesimple T, Da Meda L, Pracht M, Baroudjian B, Delyon J, Amini-Adle M, Dutriaux C, Reger de Moura C, Sadoux A, Jouenne F, Ghrieb Z, Vilquin P, Bouton D, Tibi A, Huguet S, Rezai K, Battistella M, Mourah S, Lebbe C. Phase I-II Open-Label Multicenter Study of Palbociclib + Vemurafenib in BRAF V600MUT Metastatic Melanoma Patients: Uncovering CHEK2 as a Major Response Mechanism. Clin Cancer Res. 2021 Jul 15;27(14):3876-3883. doi: 10.1158/1078-0432.CCR-20-4050. Epub 2021 May 4.
PubMed 33947696
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Multicenter, Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma With BRAFv600 Mutated and CDKN2A Loss and Expression of Rb and Treated by Vemurafenib
- ClinicalTrials.gov ID
- NCT02202200
- Acronym / sponsor ID
- OPTIMUM / D20121106
- Keywords
- Melanoma, BRAF mutated
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Nov 2016 (estimated)
- Study completion
- Aug 2018 (estimated)
- First posted
- 28 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open label multicentre, phase I-II study with tumour molecular pharmacodynamics (MPD) evaluation and pharmacokinetics of PD-0332991 added to vemurafenib in patients suffering metastatic melanoma with BR.
The main objective is to establish the Maximum Tolerated Dose (MTD) of PD-0332991 when added to standard vemurafenib therapy (960 mg BID). The estimated MTD is defined as the dose of PD-0332991 combined with vemurafenib that will be associated with a prespecified proportion of patients experiencing a Dose-Limiting Toxicity (DLT), ie, 1/3.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PD-0332991 | Experimental | Drug: PD- 0332991 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age > 18 years
- Stage IV or un-resectable stage III melanoma
- Presence of BRAF V600E/K mutation and CDNKN2A loss and expression of Rb using immunohistochemistry in a recent metastatic sample (< 6 months)
- A previous exposure to BRAF inhibitor or combination of BRAF and MEK inhibitors therapy is allowed unless it has been stopped more than 3 months before study enrolment(This will defined the two strata of the trial)
- No previous therapy by MEK inhibitor unless associated with BRAF inhibitors
Key exclusion criteria (12 listed)
- Inadequate hepatic function defined as serum bilirubin>25 μmol/l, transaminases > 3.0 times the upper limit of normal (ULN) or 5ULN in cases of liver metastases;
- Inadequate bone marrow function defined as absolute neutrophil count<1500/mcl, platelets<150000/mcl and haemoglobin<8g/dL
- Inadequate renal function with serum creatinine>2.0mg/dl) and /or creatinine clearance< 60 ml/min
- Untreated brain metastases : Patients with brain metastases will be eligible if they have completed treatment 1 months prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 5 days, and are neurologically asymptomatic
- Myocardial infarct or unstable angina within the past 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD- 0332991PD-0332991 Inhibitor of cyclin-dependant kinase (CDK) 8 schedules will be evaluated PD-0332991 PO QD either at 25 mg, 50 mg, 75 mg, 100 mg, 125 mg, 150 mg, 175 mg and 200 mg All patients will receive vemurafenib as background therapy ,bid at 720mg bid for the first group (during the first 2 cycle then 960 mg bid if good tolerance) and 960mg bid for all other patients | Drug | PD-0332991 |
Primary outcome
Occurrence within the first 2 cycles of treatment of a DLT
Time frame: 42 Days
DLTs, serious adverse events and adverse events leading to treatment discontinuations will be determined as follows: * Any grade 3 or more non-haematological toxicity excluding: * Grade 3 asymptomatic increase in liver function tests (AST, ALT, ALP) reversible within 7 days for subjects without liver involvement, or grade 4 for subjects with liver involvement. * Grade 3 vomiting if it is encountered despite adequate and optimal therapy (e.g. 5HT3 antagonists and corticosteroids). * Grade 3 diarrhoeas if encountered despite adequate and optimal anti diarrhoea therapy. * Confirmed grade 3 QTc prolongation (QTc >500 msec) that persists after correction of other possible causes such as electrolyte imbalance * Grade 4 hyperlipidemia if it is encountered despite adequate and optimal therapy. * Any grade 4 neutropenia of > 5 days duration, or febrile neutropenia lasting for more than 1 day. * Grade 4 thrombocytopenia > 1 day, or grade 3 with bleeding.
3 secondary outcomes
Efficacy
Time frame: 42 Days
1 year survival rate
Time frame: 1 year
Tolerance
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2016.
- Derived from this study: PubMed 33947696Louveau B, Resche-Rigon M, Lesimple T, Da Meda L, Pracht M, Baroudjian B, Delyon J, Amini-Adle M, Dutriaux C, Reger de Moura C, Sadoux A, Jouenne F, Ghrieb Z, Vilquin P, Bouton D, Tibi A, Huguet S, Rezai K, Battistella M, Mourah S, Lebbe C. Phase I-II Open-Label Multicenter Study of Palbociclib + Vemurafenib in BRAF V600MUT Metastatic Melanoma Patients: Uncovering CHEK2 as a Major Response Mechanism. Clin Cancer Res. 2021 Jul 15;27(14):3876-3883. doi: 10.1158/1078-0432.CCR-20-4050. Epub 2021 May 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PD- 0332991 in people with Melanoma BRAF V600E/K Mutated and CDNKN2A Loss Defined, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence within the first 2 cycles of treatment of a DLT (time frame: 42 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02202200, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2016.